Automated multi-scale computational pathotyping (AMSCP) of inflamed synovial tissue
Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting that distinct etiologies warrant specific targeted therapy which motivates a need for cost effective phenotyping tools in preclinical and clinical settings. To this end, we developed an automated multi-scale computational pathotyping (AMSCP) pipeline for both human and mouse synovial tissue with two distinct components that can be leveraged together or independently: (1) segmentation of different tissue types to characterize tissue-level changes, and (2) cell type classification within each tissue compartment that assesses change across disease states. Here, we demonstrate the efficacy, efficiency, and robustness of the AMSCP pipeline as well as the ability to discover novel phenotypes. Taken together, we find AMSCP to be a valuable cost-effective method for both pre-clinical and clinical research.
Authors
- Michael B. Brenner (ORCID: https://orcid.org/0000-0001-6202-8445)
- Jason D. Turner (ORCID: https://orcid.org/0000-0002-5423-5302)
- Kamil Slowikowski (ORCID: https://orcid.org/0000-0002-2843-6370)
- Akiko Noma
- Arthur M. Mandelin
- Anupamaa Seshadri (ORCID: https://orcid.org/0000-0001-8432-7518)
- Paul J. Utz (ORCID: https://orcid.org/0000-0003-1181-1565)
- William H. Robinson (ORCID: https://orcid.org/0000-0003-4385-704X)
- Darren Tabechian
- David L. Boyle (ORCID: https://orcid.org/0000-0002-1454-2834)
- William Apruzzese (ORCID: https://orcid.org/0000-0003-4037-6160)
- Jane H. Buckner (ORCID: https://orcid.org/0000-0002-9005-1885)
- Karen Salomon-Escoto (ORCID: https://orcid.org/0000-0002-3758-9563)
- Christopher T. Ritchlin (ORCID: https://orcid.org/0000-0002-2602-1219)
- Brendan F. Boyce (ORCID: https://orcid.org/0000-0002-3587-4854)
- Josh Keegan
- Zilong Bai (ORCID: https://orcid.org/0000-0002-3891-8015)
- Laura T. Donlin (ORCID: https://orcid.org/0000-0002-1428-090X)
- Ellen M. Gravallese (ORCID: https://orcid.org/0000-0002-0981-0996)
- Mandy J. McGeachy (ORCID: https://orcid.org/0000-0001-5029-1668)
- Jennifer H. Anolik (ORCID: https://orcid.org/0000-0002-1450-1549)
- Harris Perlman (ORCID: https://orcid.org/0000-0003-4174-608X)
- Hayley Carr (ORCID: https://orcid.org/0000-0001-7121-6624)
- Jack L. McMurray (ORCID: https://orcid.org/0000-0003-0229-8560)
- Joel M. Guthridge (ORCID: https://orcid.org/0000-0002-9308-237X)
- Fumitaka Mizoguchi (ORCID: https://orcid.org/0000-0002-3956-7122)
- Javier Rangel‐Moreno (ORCID: https://orcid.org/0000-0002-9738-1182)
- Daria M. Krenitsky
- Dana E. Orange (ORCID: https://orcid.org/0000-0001-9859-7199)
- James A. Lederer (ORCID: https://orcid.org/0000-0002-6445-252X)
- V. Michael Holers (ORCID: https://orcid.org/0000-0002-5634-7746)
- Maxwell A. Konnaris (ORCID: https://orcid.org/0000-0003-4893-1413)
- Vivian P. Bykerk (ORCID: https://orcid.org/0000-0002-1219-3845)
- Mark Alan Fontana (ORCID: https://orcid.org/0000-0002-0529-9035)
- Andrew D. Filer (ORCID: https://orcid.org/0000-0001-8164-6249)
- Nir Hacohen (ORCID: https://orcid.org/0000-0002-2349-2656)
- Kevin Wei (ORCID: https://orcid.org/0000-0002-1821-167X)
- María Gutiérrez‐Arcelus (ORCID: https://orcid.org/0000-0001-7898-7691)
- Dagmar Scheel‐Toellner (ORCID: https://orcid.org/0000-0003-2711-0464)
- Miguel Otero (ORCID: https://orcid.org/0000-0002-4945-2994)
- Matthew Brendel (ORCID: https://orcid.org/0000-0003-3417-4597)
- Chamith Y. Fonseka (ORCID: https://orcid.org/0000-0002-8924-4006)
- Joseph Mears (ORCID: https://orcid.org/0000-0002-0259-4055)
- Costantino Pitzalis (ORCID: https://orcid.org/0000-0003-1326-5051)
- Thomas Eisenhaure (ORCID: https://orcid.org/0000-0003-3999-3540)
- Yvonne Lee (ORCID: https://orcid.org/0000-0002-2105-3393)
- David Lieb (ORCID: https://orcid.org/0000-0001-7459-4719)
- H. Mark Kenney (ORCID: https://orcid.org/0000-0002-0598-3232)
- Christopher Dominic Buckley (ORCID: https://orcid.org/0000-0001-6924-6402)
- Larry W. Moreland (ORCID: https://orcid.org/0000-0003-4483-0359)
- Mina Rohani‐Pichavant
- Jennifer S. Albrecht (ORCID: https://orcid.org/0000-0003-4838-2274)
- Nida Meednu (ORCID: https://orcid.org/0000-0002-2868-3339)
- Richard D. Bell (ORCID: https://orcid.org/0000-0003-1562-3879)
- Danielle Sutherby
- Eddie A. James (ORCID: https://orcid.org/0000-0002-7217-5729)
- Edward M. Schwarz (ORCID: https://orcid.org/0000-0002-4854-9698)
- Anna Helena Jonsson (ORCID: https://orcid.org/0000-0002-9558-2474)
- Saba Nayar (ORCID: https://orcid.org/0000-0002-4350-110X)
- Gerald F. Watts (ORCID: https://orcid.org/0000-0003-2276-1524)
- Edward F. DiCarlo (ORCID: https://orcid.org/0000-0001-5775-3167)
- Soumya Raychaudhuri (ORCID: https://orcid.org/0000-0002-1901-8265)
- Jennifer P. Nguyen (ORCID: https://orcid.org/0000-0002-3055-5803)
- Deepak A. Rao (ORCID: https://orcid.org/0000-0001-9672-7746)
- Lionel B. Ivashkiv (ORCID: https://orcid.org/0000-0002-9951-0646)
- Judith A. James (ORCID: https://orcid.org/0000-0002-9574-7355)
- S. Louis Bridges (ORCID: https://orcid.org/0000-0003-3785-1389)
- Cristina Rozo
- Jennifer Seifert (ORCID: https://orcid.org/0000-0001-5851-7246)
- Fei Wang (ORCID: https://orcid.org/0000-0001-9459-9461)
- Stephen Kelly (ORCID: https://orcid.org/0000-0003-1302-2586)
- Chad Nusbaum
- Peter K. Gregersen
- Laura B. Hughes
- Gary S. Firestein
- Michael A. McNamara (ORCID: https://orcid.org/0000-0001-9870-576X)
- Justin Xiang
- James P. Dolan
Institutions
- Broad Institute (US)
- Northwestern University (US)
- Tokyo Medical and Dental University (JP)
- Hospital for Special Surgery (US)
- Brigham and Women's Hospital (US)
- Northwell Health (US)
- Pennsylvania State University (US)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Virginia Mason Medical Center (US)
- Feinstein Institute for Medical Research (US)
- Harvard University (US)
- Queen Mary University of London (GB)
- University of Massachusetts Chan Medical School (US)
- University of Pittsburgh (US)
- Palo Alto University (US)
- Cornell University (US)
- Barts Health NHS Trust (GB)
- Queen Elizabeth Hospital Birmingham (GB)
- University of Rochester Medical Center (US)
- Oklahoma Medical Research Foundation (US)
- University of Alabama at Birmingham (US)
- University of California San Diego (US)
- Chappaqua Central School District (US)
- William Harvey Research Institute (GB)
- NIHR Birmingham Biomedical Research Centre (GB)
- Benaroya Research Institute
- University of Birmingham (GB)
- Rockefeller University (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1038/s41467-024-51012-6
- Citations
- 7
- Primary Topic
- Digital Imaging for Blood Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.74
Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases